The
NUP98 gene at 11p15 is known to be fused to DDX10, HOXA9, HOXA11, HOXA13, HOXD11, HOXD13,
LEDGF, NSD1, NSD3, PMX1, RAP1GDS1, and TOP1 in various
hematologic malignancies. The common theme in all
NUP98 chimeras is a transcript consisting of the 5' part of
NUP98 and the 3' portion of the partner gene; however, apart from the frequent fusion to different homeobox genes, there is no apparent similarity among the other partners. We here report a de novo
acute myeloid leukemia with a t(11;12)(p15;q13), resulting in a novel
NUP98/HOXC13 fusion. Fluorescence in situ hybridization analyses, by the use of probes covering
NUP98 and the HOXC gene cluster at 12q13, revealed a fusion signal at the der(11)t(11;12), indicating a
NUP98/HOXC chimera, whereas no fusion was found on the der(12)t(11;12), suggesting that the translocation was accompanied by a deletion of the reciprocal fusion gene. Reverse transcription-PCR and sequence analyses showed that exon 16 (
nucleotide 2290) of
NUP98 was fused in-frame with exon 2 (
nucleotide 852) of HOXC13. Neither the HOXC13/
NUP98 transcript nor the normal HOXC13 was expressed. The present results, together with previous studies of
NUP98/homeobox gene fusions, strongly indicate that
NUP98/HOXC13 is of pathogenetic importance in t(11;12)-positive
acute myeloid leukemia.